title: Specific oncogenic activity of the Src-family tyrosine kinase c-Yes in colon carcinoma cells.
abstract: c-Yes, a member of the Src tyrosine kinase family, is found highly activated in colon carcinoma but its importance relative to c-Src has remained unclear. Here we show that, in HT29 colon carcinoma cells, silencing of c-Yes, but not of c-Src, selectively leads to an increase of cell clustering associated with a localisation of β-catenin at cell membranes and a reduction of expression of β-catenin target genes. c-Yes silencing induced an increase in apoptosis, inhibition of growth in soft-agar and in mouse xenografts, inhibition of cell migration and loss of the capacity to generate liver metastases in mice. Re-introduction of c-Yes, but not c -Src, restores transforming properties of c-Yes depleted cells. Moreover, we found that c-Yes kinase activity is required for its role in β-catenin localisation and growth in soft agar, whereas kinase activity is dispensable for its role in cell migration. We conclude that c-Yes regulates specific oncogenic signalling pathways important for colon cancer progression that is not shared with c-Src.
authors.affiliation: Institut de Recherches Servier, Croissy-sur-Seine, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Sancier
authors.forename: Aurélie
authors.initials: A
authors.lastname: Dumont
authors.forename: Audrey
authors.initials: A
authors.lastname: Sirvent
authors.forename: Ludmilla
authors.initials: L
authors.lastname: Paquay de Plater
authors.forename: Thomas
authors.initials: T
authors.lastname: Edmonds
authors.forename: Géraldine
authors.initials: G
authors.lastname: David
authors.forename: Michel
authors.initials: M
authors.lastname: Jan
authors.forename: Catherine
authors.initials: C
authors.lastname: de Montrion
authors.forename: Francis
authors.initials: F
authors.lastname: Cogé
authors.forename: Stéphane
authors.initials: S
authors.lastname: Léonce
authors.forename: Michael
authors.initials: M
authors.lastname: Burbridge
authors.forename: Alain
authors.initials: A
authors.lastname: Bruno
authors.forename: Jean A
authors.initials: JA
authors.lastname: Boutin
authors.forename: Brian
authors.initials: B
authors.lastname: Lockhart
authors.forename: Serge
authors.initials: S
authors.lastname: Roche
authors.forename: Francisco
authors.initials: F
authors.lastname: Cruzalegui
mesh_terms: D000818:Animals; D002277:Carcinoma / Q000235:genetics / Q000473:pathology*; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D003110:Colonic Neoplasms / Q000235:genetics / Q000473:pathology*; D018450:Disease Progression; D005260:Female; D055785:Gene Knockdown Techniques; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D016513:Mice, SCID; D009928:Organ Specificity / Q000235:genetics; D051575:Proto-Oncogene Proteins c-yes / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D014183:Transplantation, Heterologous; D019061:src-Family Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology
chemical_list: D051575:Proto-Oncogene Proteins c-yes; D016392:Proto-Oncogene Proteins pp60(c-src); D019061:src-Family Kinases